The haplotypes of the IRS-2 gene affect insulin sensitivity in Japanese patients with type 2 diabetes

• Published in: Diabetes research and clinical practice Vol. 68; no. 1; pp. 39 - 48
• Main Authors: Okazawa, Kayoko, Yoshimasa, Yasunao, Miyamoto, Yoshihiro, Takahashi-Yasuno, Akiko, Miyawaki, Takashi, Masuzaki, Hiroaki, Hayashi, Tatsuya, Hosoda, Kiminori, Inoue, Gen, Nakao, Kazuwa
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.04.2005
• Subjects: Diabetes Mellitus, Type 2 - genetics; Female; Genes, Dominant; Genes, Recessive; Haplotype; Haplotypes; Humans; Insulin Receptor Substrate Proteins; Insulin resistance; Insulin Resistance - genetics; Insulin-receptor substrate 2; Intracellular Signaling Peptides and Proteins; Japan; Male; Middle Aged; Obesity; Obesity - genetics; Phosphoproteins - genetics; Polymorphism, Single Nucleotide; Type 2 diabetes; Japan; Type 2 diabetes; Insulin-receptor substrate 2; Obesity; Insulin resistance; Haplotype
• ISSN: 0168-8227; 1872-8227
• DOI: 10.1016/j.diabres.2004.08.009

A commonly occurring nucleotide polymorphism of the insulin-receptor substrate 2 ( IRS-2) gene at amino acid 1057 from Glycine to Asparaginic acid (G1057D) was recently shown to be a determinant of insulin sensitivity in both glucose-tolerant individuals and those with type 2 diabetes. With respect to the latter, the IRS-2 D1057 allele increase the risk of insulin resistance among obese individuals. After we reconstructed haplotypes from the G1057D variant and the −769C/T replacement that was newly identified, we investigated the possibility that the IRS-2 gene affects insulin sensitivity in Japanese glucose-tolerant subjects ( n = 260) and type 2 diabetic patients ( n = 123). We did not find that the D1057 allele and haplotype pairs were associated with the risk of diabetes. However, type 2 diabetic patients, particularly obese patients, carrying the D1057 allele and the CA haplotype were associated with insulin resistance. Furthermore, we suggested that the TG and CG haplotypes might have a protective role against insulin resistance. This observation raises the possibility that both the IRS-2 D1057 allele and the CA haplotype are useful genetic markers for identifying obese individuals who are particularly susceptible to insulin resistance.